Natriuretic peptides: are these new links in the hepatorenal connections?

Commentary Natriuretic peptides: are these new links in the hepatorenal connections? In 1981, de Bold et al' discovered that the heart produced a peptide factor, subsequently named atrial natriuretic peptide (ANP), with potent actions affecting sodium metabolism and blood pressure. Since then, other related peptides, first brain natriuretic peptide (BNP), and more recently C type natriuretic peptide (CNP) were isolated. These peptides share sufficient similarities in structure, gene regulation, and metabolism to be grouped together as a family of peptides. It was soon realised that these hormones have multiple and varied actions beyond their natri-uretic property, that not all are natriuretic, and they may have paracrine as well as endocrine actions.2 These diverse effects are mediated through specific membrane associated natriuretic peptide receptors (NPRs), with a receptor subtype being selective for each peptide. Despite this, they have remained together as a family of natriuretic peptides. Atrial natriuretic peptide, the prototype ofthe natriuretic peptides, is secreted from the atria. ANP has potent haemodynamic and renal effects. It is natriuretic, vaso-dilatory as well as being an antagonist to the actions of the renin-angiotensin-aldosterone system, and therefore important in the regulation of blood pressure. ANP has numerous other endocrine actions in vitro and in experimental animals including inhibition ofACTH and arginine vasopressin secretions, as well as inhibition of thirst. More recently, an in vitro anti-proliferative effect of ANP on vascular smooth muscle cells has also been shown.3 Brain natriuretic peptide is something of a misnomer. Although originally isolated in the brain, its main site of synthesis is the heart. It binds to the same receptor and has similar biological effects as ANP. C type natriuretic peptide, the newest member of the natriuretic peptide family, was originally isolated from porcine brain. Little CNP is detected in cardiac tissues; in contrast, significant concentrations are found in the brain, vascular endothelium, and the kidney.4 The role of CNP as a circulating hormone remains unproved, because the plasma concentrations are low and there is little evidence to support that plasma values are subject to regulation. It therefore has been postulated to be a paracrine hormone. Despite its presence, together with its receptor in the kidney, it has no natriuretic action in humans. Recent work has directed towards identifying a vascular CNP system, with CNP exerting an anti-proliferative effect on vascular smooth muscle cells,5 thereby acting as a mediator of vascular remodelling. Thus we read with interest the …